This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The aims of this protocol are to document whether the human XMR virus is able to replicate in a model close to man, i.e. rhesus macaque. If XMRV is able to induce an active infection, what are the viral kinetics, dissemination and antiviral immune responses in this model? During the reporting period, a strong correlation was established between the infection with a newly identified gammaretrovirus related to MuLV in prostate tumors from patients exhibiting a genetic inactivation of the RNASEL pathway (R462Q) linked to type I IFN antiviral mechanism. Infection of healthy male and female rhesus macaquesd emonstrated productive transient infection but low level of viral replication in vivo. The acute viremia was accompanied by significant levels of T, B and NK cell activation in vivo as well as appearance of low but clear levels of antigen specific antibodies. T cell responses were mostly undetectable. Reinoculation with purified XMRV did not induce detectable viremia but a transient resurgence of XMRV provirus positive blood cells in vivo.